Note: Descriptions are shown in the official language in which they were submitted.
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LIGHT DELIVERY CATHETER
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority of U.S. Provisional
Application No. 60/401,063, filed August 5, 2002, and U.S. Provisional
Application
No. 60/401,065, filed August 5, 2002.
FIELD OF THE INVENTION
[0002] The invention relates to the field of medical instruments used in
administering light for therapeutic methods, such as photodynamic therapy
(PDT),
that require light illumination of target tissue. The present invention
provides
improved light delivery catheter devices that provide more uniform light
delivery by
more effectively flushing blood from the light treatment site, as well as
other features
and advantages.
I 5 BACKGROUND
[0003] PDT is a medical treatment that utilizes light activated photosensitive
dyes to
elicit a beneficial biological response. These dyes, or photosensitizers,
elicit a
biological response when irradiated with light within a certain wavelength
range but
are inert without such illumination.
[0004] A promising area for the application of PDT is in the treatment of
cardiovascular disease indications such as vulnerable plaque, atherosclerosis
and
restenosis. Such applications generally involve the delivery of
photosensitizers into a
blood vessel to be treated, followed by the delivery of light to the target
tissue, often
through a light delivery catheter. One of the challenges associated with PDT
and
other treatments employing endovascular light delivery arises from the
tendency of
blood to
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attenuate light in the treatment region. The PDT effect can be significantly
degraded if
blood is not eliminated from the light path. This adverse effect exists for
PDT methods
utilizing all wavelengths of light treatment, but is particularly significant
for treatments
using short wavelengths of light (e.g., less than 610 nm), where light
attenuation by blood
is most significant.
[0005] Balloon catheters have been used in an effort to eliminate blood during
the light
delivery process. A commonly employed approach is to place a light-emitting
fiber
within a transparent or translucent angioplasty-style balloon. Blood is
removed from the
light treatment region by inflating the balloon to displace the blood. This
approach has
been employed almost exclusively for most cardiovascular PDT methods.
[0006] For example, Spears, U.S. Patent No. 4,512,762, discloses a balloon
catheter
equipped with flexible optical fibers for transmission of light from an
external source for
illumination of the interior of the inflated balloon. By inflation of the
balloon, the blood
between the balloon and the diseased vascular wall is displaced. Other
examples of PDT
catheters employing an optical element within a displacement balloon include
the
following: Narciso, U.S. Patent Nos. 5,169,395; 5,441,497; 5,700,243; Leone,
U.S.
Patent Nos. 5,797,868; 5,891,b82; EP 0 732 085; EP 0 732 079; Ligtenberg et
al., EP 0
732 079 A1; Bower et al., U.S. Patent No. 6,013,053; 6,086,558; Overholt et
al., U.S.
Patent No. 6,146,409; Aita et al., U.S. Patent No. 6,132,423; and Amplatz et
al., U.S.
Patent No. 5,620,438.
[0007] A significant problem with the displacement balloon approach described
in the
foregoing patents is that it fails to fully displace the blood, leaving some
blood trapped
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between the outside surface of the inflated balloon and the inside surface of
the vascular
wall. With this approach, adequate displacement generally requires a balloon
that is at
least as long as the light treatment zone. To achieve a cylindrical shape that
is consistent
with the shape of the vessel being treated, non-compliant balloon materials
are typically
used, because balloons made from such materials retain their shape when
inflated. To
avoid injuries associated with mechanical trauma due to inflation of a non-
compliant
cylindrically-shaped balloon, it is necessary to inflate the balloon using a
very low
pressure. However, such a balloon inflated at low pressure usually cannot
exert sufficient
force to adequately displace the surrounding blood. Consequently, the
angioplasty
balloon can at best be a compromise solution since under-inflation prevents
mechanical
trauma without achieving adequate blood removal, whereas over-inflation
achieves better
blood removal but with increased risk of mechanical trauma.
[0008] One attempt to overcome this shortcoming of the angioplasty design
approach is
to utilize a so-called "weeping balloon" as described in Fume et al., U.S.
Patent No.
5,876,426; Leone, U.S. Patent No. 5,709,653; and Amplatz et al., U.S. Patent
No.
5,833,68 and 5,964,751. Each of these patents discloses a light delivery
catheter fitted
with a porous angioplasty-style balloon that leaks fluid from its surface to
flush blood
from around the periphery of the balloon. Though such weeping balloons may
provide
better blood elimination than standard angioplasty-style balloons, they suffer
from some
significant shortcomings. For example, flushing fluid delivered in such a
manner tends to
find the path of least resistance to escape into the open blood vessel,
leaving pockets of
blood trapped between the balloon and the vessel wall. Another limitation is
that when
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the balloon is deflated blood can be sucked into the balloon where it will
attenuate light
delivered in subsequent inflation and treatment cycles.
[0009] Other shortcomings of both the standard displacement balloon and the
weeping
balloon approaches can arise from the use of non-compliant balloon materials.
Each of
the patents referenced above generally discloses a light delivery catheter
having an
elongated, tubular balloon that extends along the length of the catheter at
least as long as
the length of the light treatment zone. As explained by Saab, in "Applications
of High-
Pressure Balloons in the Medical Device Industry," published in Medical Device
and
Diagnostic Industry, Sept. 2000, pg. 86, achieving this tubular shape in an
inflated
balloon generally requires the use of a relatively non-compliant (i.e., Iess
elastic) balloon
material that will retain its shape when inflated. Because non-compliant
balloons are
more rigid and do not conform to the shape of the vessel, such balloons have a
greater
tendency to cause mechanical trauma to the vessel. The resulting injury
response can
lead to restenosis.
[0010] The non-compliant angioplasty balloon is also limited in its ability to
treat long
tortuous vessels. When using a light emitting element within an angioplasty
balloon it is
necessary to fully inflate the balloon to adequately displace blood. However,
this can be
difficult in tortuous vessels, especially if the treatment length is greater
than 1-2 cm. This
is due to the fact that, when inflated, the non-compliant angioplasty balloon
tends to
inflate in a straight line, rather than follow the curvature of the vessel.
The result is that
the balloon tends to straighten the vessel, causing mechanical trauma to the
vessel.
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[0011] The non-compliant angioplasty balloon also has a limited ability to
treat small
diameter vessels. When using the angioplasty balloon approach, it is necessary
to mount
the non-compliant angioplasty balloon on the catheter shaft overlapping the
light
treatment zone. However, use of such a non-compliant balloon adds to the
diameter of
the device in the treatment zone, thereby limiting access to small vessel
diameters.
[OOI2] Still another shortcoming of the non-compliant angioplasty balloon is
in the
treatment of vessels whose diameter tapers or otherwise changes within the
length of the
section to be treated. When using an angioplasty style balloon it is necessary
to inflate
the balloon to displace the blood. This can cause injury within the smaller
diameter
regions of the vessel being treated since these balloons generally have a
constant
diameter along their length.
[OOI3] Furthermore, non-compliant balloon devices have a limited ability to
treat
multiple vessel diameters .with a single device. With the angioplasty balloon
approaches,
the device generally must be correctly sized to the vessel to be treated. This
requires that
a significant stock of devices be kept on hand and also limits the various
vessel
geometries that can be treated.
[0014] Thus, there is a significant need for improved light delivery catheters
that can
provide improved blood elimination along the Light treatment region and can
avoid the
shortcomings associated with prior devices employing non-complaint angioplasty
balloons. The present invention provides improved light delivery catheters
having these
and other features and advantages.
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SUMMARY
[0015] The present invention provides improved light delivery catheters for
use in
therapeutic methods, such as PDT, that require illumination of target tissue
within a
blood vessel or other hollow body organ. An improved catheter comprises a
catheter
shaft having a light treatment zone at its distal end. A light guide, such as
an optical
fiber, in the catheter shaft transmits light from a light source at the
proximal end of the
catheter shaft to the light treatment zone. An occlusion balloon is positioned
on the distal
end of the catheter shaft adjacent to the light treatment zone. An inflation
lumen in the
catheter shaft, and in fluid communication with the balloon, delivers fluid
from an
inflation fluid source at the proximal end of the catheter shaft to the
balloon. An inftision
lumen in the catheter shaft delivers infusion fluid from an infusion fluid
source at the
proximal end of the catheter shaft to the light treatment zone. A plurality of
infusion
ports formed on the light treatment zone, and in fluid communication with the
infusion
lumen, deliver infusion fluid to the hollow body organ so that blood can be
flushed from
the region between the light treatment zone and target tissue.
[0016] The invention also provides light delivery catheters having features to
allow
detection of emitted Light. In one embodiment, the catheter has a light
delivery optical
fiber having a distal end terminating in the light treatment zone. A second
light detection
optical fiber in the catheter shaft detects light emitted by the first optical
fiber and
transmits the detected light to the proximal end of the catheter shaft. In
another
embodiment, a fluorescent material is incorporated into the distal end of the
catheter shaft
to provide a fluorescent emission when exposed to light emitted from the
optical fiber.
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This emission can propagate back to the proximal end of the optical fiber to
allow
monitoring of light delivery.
[0017] Another aspect of the invention provides improved infusion lumens for
use with
light delivery catheters. In one embodiment, the infusion lumen has a larger
diameter at
the proximal end of the catheter than at the distal end. The transition
between the larger
and smaller diameter generally occurs at the distal end of the catheter,
proximal to the
light treatment zone. This approach allows much higher flow rates to be
achieved for a
given pressure than would otherwise be possible if the diameter of the
infusion lumens
near the proximal end were the same as those near the distal end, where the
shaft
diameter is relatively small.
DRAWINGS
[0018] These and other features, aspects and advantages of the present
invention will
become more fully apparent from the following detailed description, appended
claims,
and accompanying drawings where:
FIG. lA schematically illustrates a side view of the distal end of a Iight
delivery
catheter;
FIG. 1B is a cross-sectional view of the light delivery catheter of FIG. lA,
with
the plane of the cross-section coincident with the location on the shaft were
discrete flush
ports have been created on the periphery of the shaft;
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FIG. 2 schematically illustrates a side view of the proximal end of the light
delivery catheter of FIG. lA;
FIG. 3A schematically illustrates a side view of a back-flush embodiment of a
light delivery catheter;
FIG. 3B is a cross-sectional view of the light delivery catheter of FIG. 3A;
FIG. 4A schematically illustrates a shaft cross-section of an embodiment of a
light
delivery catheter where fiber and guidewire are adjacent to each other;
FIG. 4B schematically illustrates a shaft cross-section of an embodiment of a
light
delivery catheter in which a single lumen is used for both fiber and
guidewire;
FIG. 4C schematically illustrates a shaft cross-section of an embodiment of a
light
delivery catheter in which three infusion lumens are oriented at 120 degrees
around the
periphery of the catheter shaft;
FIG. SA schematically illustrates a side view of a light delivery catheter
having a
rapid exchange guidewire port proximal to the light treatment zone;
FIG. SB is a cross-sectional view of the light delivery catheter of FIG. SA;
FIG. 6A schematically illustrates a side view of a light delivery catheter
having a
rapid exchange guidewire port distal to the light treatment zone;
FIG. 6B is a cross-sectional view of the light delivery catheter of FIG. 6A in
the
region proximal to the rapid exchange port;
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FIG. 7A schematically illustrates a side view of a light delivery catheter
having a
centering balloon over the light treatment zone;
FIG. 7B is a cross-sectional view of the light delivery catheter of FIG. 7A;
FIG. 8A schematically illustrates a side view of a light delivery catheter
having an
angioplasty balloon over the light treatment zone;
FIG. 8B is a cross-sectional view of the light delivery catheter of FIG. 8A;
FIG. 9A schematically illustrates a side view of a light delivery catheter
having
perfusion ports;
FIG. 9B is a cross-sectional view of the light delivery catheter of FIG. 9A;
FIG. l0A schematically illustrates a side view of a light delivery catheter
having a
fiber for light detection;
FIG. 1 OB is a cross-sectional view of the light delivery catheter of FIG.
10A;
FIG. 11A schematically illustrates a side view of a tapering catheter shaft
design;
FIG. 11B is a cross-sectional view of the light delivery catheter of FIG. 11A
proximal to the transition;
FIG. 11C is a cross-sectional view of the light delivery catheter of FIG. 11A
distal
to the transition;
FIG. 12A schematically illustrates a side view of a light delivery catheter
having
infusion lumens terminating in infusion ports proximal to the light delivery
zone;
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FIG. 12B is a cross-sectional view of the light delivery catheter of FIG. 12A
proximal to the transition;
FIG. 12C is a cross-sectional view of the light delivery catheter of FIG. 12A
distal
to the transition;
FIG. 13A schematically illustrates a side view of another embodiment of a
light
delivery catheter having infusion lumens terminating in infusion ports
proximal to the
light delivery zone;
FIG. 13B is a cross-sectional view of the light delivery catheter of FIG. 13A
proximal to the transition;
FIG. 13C is a cross-sectional view of the light delivery catheter of FIG. 13A
distal
to the transition;
FIG. 14A schematically illustrates a side view of a light delivery catheter
having
one infusion lumen terminating proximal to the light treatment zone and a
second
infusion lumen continuing throughout the light treatment zone to provide
multiple
infusion ports along the length of the light treatment zone;
FIG. 14B is a cross-sectional view of the light delivery catheter of FIG. 14A
proximal to the transition;
FIG. 14C is a cross-sectional view of the light delivery catheter of FIG. 14A
distal
to the transition;
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FIG. 15A schematically illustrates a side view of a back-flush embodiment of a
light delivery catheter having an infusion lumens terminating in infusion
ports distal to
the light delivery zone;
FIG. 15B is a cross-sectional view of the light delivery catheter of FIG. 15A
proximal to the transition;
FIG. 15C is a cross-sectional view of the light delivery catheter of FIG. 15A
distal
to the transition;
FIG. 16A schematically illustrates a side view of a light delivery catheter
with an
outer shaft forming infusion lumens terminating proximal to the light
treatment zone;
FIG. 16B is a cross-sectional view of the light delivery catheter of FIG. 16A
proximal to the transition;
FIG. 16C is a cross-sectional view of the light delivery catheter of FIG. 16A
distal
to the transition;
FIG. 17A schematically illustrates the distal end of a back-flush version of a
light
delivery catheter having infusion lumens terminating at the distal end of the
light
treatment zone;
FIG. 17B is a cross-sectional view of the light delivery catheter of FIG. 17A
proximal to the transition;
FIG. 17C is a cross-sectional view of the light delivery catheter of FIG. 16A
distal
to the transition;
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FIG. 1 ~ schematically illustrates a side view of a second embodiment of the
proximal end of a light delivery catheter; and
FIG. 19 schematically illustrates a side view of a third embodiment of the
proximal end of a light delivery catheter.
[0019] For simplicity and clarity of illustration, the drawing figures
illustrate the
general elements of the light delivery catheters. Drawings of catheter
assemblies are to
schematically illustrate the general position of elements within the devices.
Description
and details of well-known features and techniques are omitted to avoid
unnecessarily
obscuring the invention.
DESCRIPTION
[0020] The present invention provides a light delivery catheter having an
occlusion
style balloon with a fluid flush, which provides superior performance over
previous
devices. In the treatment approach described herein, an occlusion balloon is
inflated on
one or both sides of the light treatment zone to block blood flow, after which
a flushing
fluid is infused to flush blood away from the light treatment zone. This
approach can be
used for application of PDT in cardiovascular indications to inhibit,
stabilize and/or
reduce occlusions within the cardiovascular system, including treatment of
such
conditions as vulnerable plaques, atherosclerosis, restenosis, intimal
hyperplasia and
aneurysm.
[0021] FIGS. lA and 1B illustrate an embodiment of the distal end of an
improved light
delivery catheter for use in therapeutic methods, such as PDT, that require
light
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illumination to target tissue within a blood vessel or other hollow body
organ. The
catheter comprises an elongated tubular catheter shaft 2 having a proximal end
3 (shown
in FIG. 2) which remains outside of the body organ when in use and a distal
end 1, which
is inserted into the body organ when in use. The distal end I has a light
treatment zone 6
through which light can be transmitted. The catheter shaft preferably includes
a
guidewire lumen 18 to allow the distal end 1 of the catheter to be advanced
over a guide
wire through the body organ until the light treatment zone 6 is adjacent to
the target
tissue. A light guide 7 in the catheter shaft 2 transmits Iight from a light
source (not
shown) at the proximal end 3 of the catheter shaft 2 to the light treatment
zone 6. An
occlusion balloon 8 is positioned on the distal end 1 of the catheter shaft 2
adjacent to the
light treatment zone 6. An inflation lumen 14 in the catheter shaft 2 is in
fluid
communication with the balloon 8. Inflation Iumen 14 delivers fluid from an
inflation
fluid source (not shown) at the proximal end 3 of the catheter shaft 2 to the
balloon 8.
Inflation lumen 14 can also serve as a lumen for housing light guide 7. One or
more
infusion lumens 4 in the catheter shaft 2 deliver infusion fluid from an
infusion fluid
source (not shown) at the proximal end 3 of the catheter shaft 2 to the light
treatment
zone 6. A plurality of infusion ports 5 are formed on the light treatment zone
6 and are
in fluid communication with the infusion Iumens 4. Infusion fluid is delivered
to the
hollow body organ through infusion ports 5, so that blood or other opaque
material in the
hollow body organ can be flushed from region between the light treatment zone
6 and the
target tissue. Intermediate point l0a on the distal end 1 connects to
intermediate point
lOb at the proximal end 3 of the catheter (shown in FIG. 2).
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[0022] FIG. 2 illustrates an embodiment of the proximal end 3 of the catheter.
When in
use, the proximal end 3 remains outside of the hollow body organ. The proximal
end 3
includes an inflation input port 40, which communicates with the combined
fiber/inflation Lumen 14 (shown in FIGS. 1A and 1B). Optical fiber connector
52
connects to a light source (not shown) to deliver light to light guide 7
(shown in FIG.
lA). A common input port for guidewire and infusion 41 communicates with the
infusion lumens 4 and guidewire lumen 18 (shown in FIGS. lA and 1B). A
guidewire is
inserted into guidewire lumen 18 through common input port 41. Infusion fluid
is input
into infusion lumen 4 through common input port 41.
[0023] Referring again to FIGS. lA and 1B, light guide 7 is preferably an
optical fiber
but can be any means of transmitting light from the proximal end 3 of the
catheter to the
light treatment zone 6, such as an optical wave guide. The length of the light
treatment
zone 6 is preferably greater than 0.5 cm and includes a diffuser 15 for
delivering diffuse
light over an extended length. Diffuser 15 can be a modified optical fiber or
a fiber
tipped with a light diffusing element, which in either case are configured to
emit light in a
direction substantially orthogonal to the axis of catheter shaft 2.
Fiber/inflation lumen 14
preferably contains an optical fiber, which is fabricated, for example, of
plastic or glass.
The fiber runs from the connector 52 at the proximal end 3 of the catheter
shown in FIG.
2, to the distal end 1 to deliver light within the light treatment zone 6. The
fiber
terminates in a diffuser section 15 to allow light to be delivered along the
length of the
light treatment zone 6. A diffuser tip incorporating a diffusing fiber is
described, for
example, in Heath et al., U.S. Patent No. 6,366,719, and one incorporating a
diffuser
attached to the end of a fiber is described, for example, in Doiron et al.,
U.S. Patent No.
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5,269,777, both of which are incorporated by reference herein in their
entirety.
Alternatively, a fiber can be configured to emit light substantially from its
tip in an
isotropic manner. This fiber can be inserted into the fiber/inflation~lumen 14
and
mechanically drawn back and forth to deliver light along the length of the
Iight treatment
zone. Similarly, other light emitting elements such as LED's can be located
within the
light treatment zone. The device also includes means to deliver light at the
proximal end
3 of the catheter, shown in FIG. 2 such that the light input at the optical
fiber connector
52 exits from the light treatment zone 6 of the catheter to irradiate the
desired target
tissue.
[0024) The occlusion balloon 8 is preferably a compliant (elastomeric)
balloon, made
of a relatively low durometer material, such as latex, C-flex, polyisoprene,
low durometer
polyurethane, or other low durometer polymer material, with a minimal wall
thickness,
but can also be a non-compliant (semi-resilient) balloon. It can be located at
the proximal
end of the light treatment zone 6 as illustrated in FIG. lA. Alternatively,
the occlusion
balloon 8 can be located at the distal end of the light treatment zone 6 as
illustrated in the
backflush configurations shown in FIGS. 3A, 15A, and 17A. Though the drawings
show
only a singe inclusion balloon by way of example, there can also be two
occlusion
balloons, one on either end of the light treatment zone 6.
[0025) Fiber/inflation lumen 14 runs the length of the catheter and terminates
at one or
more inflation ports 17 within the occlusion balloon 8 to allow it to be
inflated. A means
for inflating the occlusion balloon 8 can be attached to the fiber/inflation
lumen 14 at the
proximal end 3 of the catheter by means of inflation port 40 (shown in FIG.
2). In the
illustrated embodiment, the inflation lumen and the lumen that contains the
optical fiber
CA 02495562 2005-02-02
are combined in a common lumen. In this approach, if a proximal occlusion
balloon is
used, a means to block fluid flow can be provided so that fluid used to
inflate the
occlusion balloon 8 cannot reach the diffuser section in the light treatment
zone 6. This
approach is advantageous when the diffuser has been designed to function in an
air
interface, as opposed to a liquid interface. Alternatively, separate gidewire
and inflation
lumens can be used.
[0026] The catheter can include a pop-off valve (not shown) at the proximal
end 3 of
the device, the pop-off valve being placed between the inflation port 40 shown
in FIG. 2
and the actual inflation device such that it is in fluid communication with
the inflation
lumen I4. The pop-off valve prevents over-inflation of the occlusion balloon
8. Use of a
pop-off valve is particularly advantageous when using a partially compliant
occlusion
balloon (e.g., polyurethane) or a non-compliant occlusion balloon (e.g.,
nylon). A
pressure meter (not shown) can also be provided at the proximal end 3 of the
device and
connected to the inflation port 40 and in fluid communication with the
inflation lumen
14. The pressure meter is located between the inflation port 40 and the
balloon inflation
device to allow the user to control inflation of the balloon 8 and to prevent
over-inflation
that could damage the vessel. Alternatively, occlusion balloon 8 can be
inflated with a
controlled volume of fluid delivered through inflation port 40 using a
calibrated syringe
or other suitable means.
[0027] Though not shown in the drawings, an infusion port can be located on
the
catheter shaft 2 adjacent and proximal to the occlusion balloon 8 to verify
inflation. In
this case, the infusion port has a dedicated infusion lumen. Angiographic
contrast media
can be infused through this port. If the balloon is inflated, the angiographic
contrast
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media infused through this port can be seen, under angiographic visualization,
to pool
proximal to the occlusion balloon. If the balloon is not sufficiently
inflated, the
angiographic contrast media will be seen, under angiographic visualization, to
flow past
the occlusion balloon. If a distal occlusion balloon is being used for
occlusion the extra
infusion port is not necessary since the existing infusion ports can serve
this same
function.
[0028] Referring again to FIGS. lA and 1B, one or more infusion lumens 4 run
the
length of the catheter from proximal end 3, terminating at one or more
infusion ports 5
within light treatment zone 6 to allow a substantially transparent or
translucent infusion
fluid to be infused into the treatment site, thereby eliminating blood from
the region
between the light treatment zone 6 and the target tissue. The infusion
flushing fluid is
preferably transparent or translucent at the wavelength used in PDT. Various
types of
infusion fluid are acceptable, including sterile saline based solutions and
electrolyte
balanced solutions. Infusion fluid is injected into the infusion lumens 4 at
the proximal
end 3 of the catheter and exits from the infusion ports 5 at the distal end 1
of the catheter.
One means for providing an infusion port is to punch a hole from the outside
of the
catheter shaft to access an infusion lumen. Other methods of forming infusion
ports can
be used as well. In some drawings only a single infusion port is shown per
infusion
lumen. However, multiple ports can be used in all embodiments where the
infusion
lumen 4 spans the light treatment zone 6 and these ports can be located along
the length
of the lumen so that they can span the length of the light treatment zone 6
and extend
beyond it.
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[0029] The use of multiple infusion ports along the length of the light
treatment zone 6
minimizes the chance of semi-stagnant blood pools being trapped in the region
surrounding the light treatment zone 6, thereby significantly increasing the
rate and
efficiency by which blood is cleared. This design also helps to eliminate
blood much
more quickly and efficiently than when flush is introduced at only a fixed
position along
the length of the catheter. This is true even when the flush rate delivered
from the single
fixed position is equal to the combined total flush rate from all infusion
ports along the
length of the catheter. This may be particularly advantageous when treating
coronary
arteries where occlusion times and flush volumes should be kept to a minimum.
[0030] The embodiment illustrated in FIGS. lA and IB comprises nine infusion
ports 5
distributed longitudinally along the light treatment zone in three sets of
three. Each set of
three ports is positioned around the circumference of the catheter shaft at
intervals of
about 120 degrees of substantially uniform radial separation, such that the
pressure of
infusion fluid passing through the ports is generally equalized about the
circumference.
A similar effect can be achieved by using more or less ports radially
distributed at each
longitudinal position, with more or less radial separation. In a preferred
embodiment, the
three infusion ports closest to the occlusion balloon 8 have a diameter of
approximately
.008 inches, and the other six distal ports have a diameter of approximately
.007 inches.
[0031] However, there are a multitude of infusion port diameters, infusion
lumen
diameters, pressure conditions, fluid velocities and infusion port
arrangements that can
achieve desired flush along the length of the light treatment zone when using
such
multiple port approaches. For example, the infusion ports can decrease in size
with the
largest holes located near the proximal end of the light treatment zone and
the smallest
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holes located near the distal end of the light treatment zone. Alternatively,
the infusion
ports can increase in size along the length of the light treatment zone. The
rate of
infusion can also be varied along the length of the light treatment zone by
varying the
density of the infusion ports. The density of the ports can be increased to
the point that
the infusion lumen becomes essentially porous throughout the length of the
light
treatment zone. Alternatively, flush pressure can be varied along the length
of the light
treatment zone by using different lumens each having ports located at
different locations
along the length of the light treatment zone and with each lumen receiving
different
pressures. Alternatively, this same effect can be achieved by using lumens
with different
diameters such that the lumens provide different flow rates at the distal end
of the device.
In these and similar ways, the output can be modified to preferentially
deliver flush fluid
near the proximal end, near the distal end or uniformly along the length of
the device. In
the case of infusion ports being fed from a common lumen, various flow rates
can be
delivered from the various ports by varying the size of the opening of the
ports. The
particular details of how to size the holes and their location is a function
of the diameter
of the infusion lumen, the desired infusion pressure used, the amount of flush
desired and
how the flush is to be delivered, i.e., proximally loaded, distally loaded or
uniform along
the length of the light treatment zone. For example, when the diameter of the
infusion
ports is sufficiently small relative to the diameter of the infusion lumen,
there can be a
tendency for fluid flowing in the infusion lumen to continue along its flow
path toward
the distal end of the device with relatively little fluid being infused from
the proximal
infusion ports. However, at the distal end there may be a buildup of pressure,
resulting in
a higher flow rate from the most distal port, even when proximal ports are of
the same
19
CA 02495562 2005-02-02
diameter. Alternatively, at other pressure conditions or when the infusion
port diameter
is sufficiently large relative to the diameter of the infusion lumen, there is
a tendency for
a higher flow rate from the more proximal ports, even when all ports are of
the same
diameter.
(0032] For a device having a proximal occlusion balloon, with infusion
delivered along
the length of the light treatment zone, the first infusion port is generally
located just distal
to the balloon with the last port near the distal end of the light treatment
zone. For
devices with a distal balloon, the first infusion port is generally located
near the proximal
end of the light treatment zone and the last port is just proximal to the
balloon. A typical
spacing is 0.05 to 2 cm, although this spacing may be varied. For example, if
it is desired
to used a low pressure device for infusion of saline, the infusion ports that
deliver this
flush can be spaced closer together to decrease the total flow resistance.
Alternatively,
closer spacing may be used when using catheters having very small diameters
designed
for treating short lengths, such as in neurological applications. When using
larger
diameter catheters designed for treating long vessel lengths such as in
femoral arteries,
the hole spacing may be increased.
[0033] Additional infusion ports can be added around the periphery of the
device to
improve flushing. For example, two ports located on opposite sides of the
catheter
provide an improvement while three infusion ports located nominally at 120
degree
intervals around the periphery of the catheter can provide even further
improvement if the
application allows a shaft diameter sufficiently large to accommodate such a
number of
channels. As illustrated in FIG. 1B, two infusion lumens 4 can be oriented
about the
periphery of the catheter shaft 2 to provide fluid to infusion ports located
around the
CA 02495562 2005-02-02
periphery of the catheter shaft but spaced at 120 degree intervals. As
illustrated in FIG.
4C, three infusion lumens 4 can be oriented about the periphery of the
catheter shaft 2 to
provide fluid to infusion ports located around the periphery of the catheter
shaft but
spaced at 120° intervals . This improvement appears to be due, in part,
to the tendency of
the flush fluid to push the catheter away from the vessel wall, which provides
a gap so
that flush fluid can more efficiently flow along this gap and thereby improve
the flushing
efficiency.
[0034] Drugs can be delivered locally to the vessel through the catheter using
one of the
infusion lumens 4. For example, when delivering a photosensitizer drug for
PDT, the
drug can be delivered to the treatment site via an infusion Iumen 4. Next
saline or a
similar low viscosity, essentially transparent fluid is injected via the
infusion lumen 4 in
order to clear any blood or drug from the treatment site. Following this step,
light can be
delivered to the target tissue via light treatment zone 6.
[0035] The catheter shaft 2 is preferably made of a transparent or translucent
material,
at least in the region of the light treatment zone 6, this material having
minimal light
absorption at the wavelength used in the PDT treatment. However the shaft 2
may
contain a material that causes significant optical scattering. The shaft is
preferably
constructed of a polymer or layers of polymer and may contain a reinforcing
structure
such as a braid or mesh. Radiopaque marker bands (not shown) can be added to
aid in
positioning under angiography. The bands are preferably located at the
proximal and
distal ends of the diffuser 15, such that both the light treatment zone 6 and
occlusion
balloon 8 can be correctly positioned. A marker band can also be located on
the shaft 2
21
CA 02495562 2005-02-02
within the occlusion balloon 8 or on the shaft 2 next to the occlusion balloon
8 but on the
side opposite the light treatment zone 6.
[0036] FIGS. 4A, 4B and 4C illustrate various alternative lumen
configurations. As
illustrated in FIG. 4A, the fiber can be contained within a common
fiber/inflation lumen
14 in the shaft allowing the fiber to be fully integrated into the device with
the fiber lying
parallel to the guidewire and with the guidewire lumen 18 extending over the
entire
length of the device. When using an occlusion balloon located proximal of the
light
treatment zone, a fluid seal (not shown) can be placed in the fiber/inflation
lumen 14
between the occlusion balloon 8 and the light treatment zone 6 to prevent
fluid from
coming in contact with the diffuser 15.
[0037] It should be understood that the various lumens can be provided
separately or
combined in various configurations. As referenced herein, the term "inflation
lumen"
refers generally to any lumen that carnes inflation fluid, even if it is also
used for other
purposes, such as a fiber or guidewire lumen. Likewise, the term "fiber lumen"
refers
generally to any lumen that can house an optical fiber or other light guide
and the term
"guidewire lumen" refers generally to any Iumen through which a guidewire is
run, even
if the lumens are combined or serve another purpose. And the term "infusion
lumen"
refers generally to any lumen through which infusion fluid is transported,
even if the
lumen is combined with another lumen or serves another purpose.
[0038] Another embodiment illustrated in FIG. 4B, has a common guidewire and
fiber
lumen 22. The fiber is not integrated into the device in this design but
rather the device is
first passed over the guidewire and positioned within the body, the guidewire
is then
22
CA 02495562 2005-02-02
removed and the optical fiber is inserted into a guidewire/fiber lumen 22. In
this case the
guidewire/fiber lumen 22 runs essentially the entire length of the device. A
separate
inflation lumen 16 is provided.
[0039] The fiber can also be contained within its own lumen in the shaft and
having a
separate lumen for balloon inflation. FIG. 4C illustrates an alternative shaft
cross section
for an embodiment in which three infusion lumens 4 are oriented at 120 degrees
around
the periphery of the catheter shaft 2. This embodiment provides a separate
fiber lumen
13 and inflation lumen 16.
[0040] The lumen configurations shown in FIGS. 4A, 4B and 4C are given as
examples
but are not intended to be an exhaustive list. For example, the fiber and
infusion lumens
can be combined into a single lumen. The guidewire and infusion lumens can be
combined into a common lumen. Alternatively, the fiber, guidewire and infusion
lumens
can be combined into a single lumen. In the case of the infusion lumens,
multiple lumens
can be used that are oriented around the periphery of the catheter shaft.
Alternatively,
these separate lumens can be connected such that they are in fluid
communication with
each other along the entire length of the device.
[0041] The guidewire lumen can be designed to accommodate a rapid exchange
mode.
A typical example is illustrated in FIGS. SA and SB using a single proximal
occlusion
balloon. The guidewire lumen 18 originates at a rapid exchange guidewire port
24
proximal to the light treatment zone 6 and occlusion balloon 8. As illustrated
in FIGS.
6A and 6B, a rapid exchange port 24 can also be located distal of the light
treatment zone
and with a single occlusion balloon 8 proximal to the light treatment zone 6.
23
CA 02495562 2005-02-02
[0042] Any of the embodiments described herein can include one or more
centering
balloons located approximately within the light treatment zone 6. An example
of a light
delivery catheter including a centering balloon is illustrated in FIGS. 7A and
7B. The
centering balloon 25 is preferably made of a non-compliant material such as
nylon, PET
or high durometer polyurethane, such that it has a well-defined diameter when
inflated.
The centering balloon is inflated through inflation lumen 16 and inflation
port 27. In this
embodiment, the centering balloon 25 is connected to an inflation lumen 16
that is
common with the occlusion balloon 8. Alternatively, the centering balloon and
occlusion
balloon can be inflated using separate inflation lumens. The centering balloon
25
preferably has a diameter that is slightly less than the vessel diameter. When
inflated, the
centering balloon 25 holds the catheter shaft 2 away from the vessel wall to
improve light
dose uniformity. It is preferably made of a sufficiently non-compliant
material such that
its inflated diameter is restricted to prevent it from causing significant
injury to the
vessel. Preferably, the inflated diameter and inflated pressure are such that
a saline
infusion fluid can flow past the centering balloon 25.
[0043] In another embodiment illustrated in FIGS. 8A and 8B, a non-compliant
angioplasty balloon 30 is positioned over light treatment zone 6. The
angioplasty balloon
30 allows the device to be used as an angioplasty device to mechanically open
the vessel
and/or deliver a stmt. When an angioplasty balloon is used, another inflation
lumen 29
dedicated to the angioplasty balloon 30 is preferably added to accommodate the
high
pressures that axe generally used in such balloons. The example shown in FIGS.
8A and
8B provides a means for drug delivery (via the infusion lumen 4), angioplasty
and light
delivery. When used to deliver drugs that are not readily taken up within the
target
24
CA 02495562 2005-02-02
tissue, both proximal and distal occlusion balloons can be used to trap the
drug between
the balloons and thereby increase their contact time with the vessel wall to
improve the
efficiency of drug delivery. When an angioplasty balloon is used in this
manner, infusion
ports can be located both proximal and distal to the angioplasty balloon.
[0044] As illustrated in FIGS. 9A and 9B, the guidewire lumen 18 can function
as a
perfusion channel. Perfusion ports 32 are created proximal to the light
treatment zone 6
and proximal to any occlusion or light treatment balloons. The perfusion ports
32 allow a
limited amount of blood to flow from outside the catheter into the guidewire
lumen 18.
When the guidewire is retracted, blood enters the perfusion ports 32 and flows
down the
guidewire lumen 18 and exits out the distal end of the device. In this way,
blood can
flow past the occlusion balloon 8 and light treatment zone 6 even when the
occlusion
balloon 8 is inflated. However, the blood is confined within the catheter
shaft 2 such that
light absorption by the blood is minimal.
[0045] FIGS. l0A and l OB illustrate another embodiment of the light delivery
catheter,
which includes a light detection fiber 34. This light detection fiber 34 is
constructed
with scattering material at its distal end, which allows light that is emitted
from the
diffuser 15 to enter the second light detection fiber 34. This light
propagates within this
light detection fiber 34 positioned within detection fiber lumen 35 from the
distal end 1
of the catheter back to its proximal end 3. Monitoring means (not shown) are
provided at
the proximal end of the light detection fiber 34, which allow its optical
output power to
be measured, thereby providing a means of monitoring the power that is being
delivered
at the distal end 1 of the device. This monitor can be calibrated before the
catheter is
inserted into the body to provide a calibrated means of monitoring output
power.
CA 02495562 2005-02-02
[0046] A small amount of fluorescent material can be incorporated at the
distal end of
this second light detection fiber 34. The emission characteristics of this
fluorescent
material are such that when it is irradiated with the wavelength used for the
PDT
treatment, it emits fluorescence at a different wavelength. This fluorescent
material can
be made of an inorganic ground crystalline material that absorbs one
wavelength and
emits a second wavelength which is typically longer than the incident
wavelength. An
inorganic may be used since such materials tend to be more stable and less
likely to
photobleach. This fluorescent emission can be detected at the proximal end of
the light
detection fiber 34, thereby providing a means of monitoring optical dose being
delivered
to the treatment site. The detection means can include a narrowband filter to
pass the
fluorescent wavelength and rej ect extraneous wavelengths, particularly the
wavelength
used for PDT excitation.
[0047] The fluorescent material can also be incorporated at the distal end of
the diffuser
15. This embodiment can be used to provide detection without the second
detection fiber
34. Light that reaches the distal end of the diffuser 15 generates
fluorescence, some of
which propagates back to the proximal end of the fiber 7. This fluorescence,
being of a
different wavelength than the PDT treatment light, can be separated using a
dichroic
beam sputter or similar wavelength selective optical element. Once separated
from the
PDT treatment wavelength, the fluorescence can be detected and used to monitor
the
delivered power in a manner similar to that described above.
[0048] Another aspect of the invention provides improved infusion lumens for
use with
light delivery catheters. For treatment of small vessels in which the distal
end of the
catheter must have a low cross sectional area, a smaller diameter catheter
shaft with
26
CA 02495562 2005-02-02
smaller diameter infusion lumens is preferable. However, small diameter
infusion
lumens can make it difficult to deliver sufficient pressure at the distal end
of the catheter
to provide adequate flush. This can be overcome by using a catheter shaft
design that has
larger diameter infusion lumens near its proximal end and smaller diameter
lumens near
its distal end. The larger diameter infusion lumens in the proximal region
allow a higher
pressure to be provided at the distal end of the catheter to maintain the flow
of the infused
flushing fluid at the distal end. One embodiment of this concept is
illustrated in FIG.
1 lA. As shown in that figure, the cross section of the infusion lumens is
relatively large
at the proximal end of the catheter with those lumens tapering down to a
smaller diameter
in a region proximal of the light treatment zone. The particular point at
which this
transition occurs is not critical, as long as the infusion lumens have the
larger diameter
along the majority of the length of the catheter. V~hile FIG. 1 lA shows the
lumens with a
gradual taper, the desired outcome can also be achieved by using a proximal
shaft having
larger diameter infusion lumens and a distal shaft having smaller diameter
infusion
lumens and butt welding these two shafts together at a point proximal of the
light
treatment zone.
[0049] As shown in FIGS. 11A, 11B and 11C, the catheter shaft 2 is provided
with a
variable diameter which forms a narrowing transition 39 proximal to the light
treatment
zone 6. The narrowing transition 39 reduces the diameter of the catheter shaft
2 and the
diameter of the infusion lumens proximal to the light treatment zone 6,
allowing the distal
end to be easily inserted into a narrow vessel. The catheter shaft 2 comprises
one or more
infusion lumens 4 having a variable diameter. The diameter of the infusion
lumens 4
decreases at the transition 39 of the catheter shaft 2, such that the infusion
lumens have a
27
CA 02495562 2005-02-02
constricted portion along the light treatment zone. Such a configuration
allows desired
infusion flow rates to be achieved while maintaining relatively low pressures,
even when
the distal tip of the device is relatively small. As used herein, the term
"narrowing
transition" refers generally to any means of reducing the diameter of the
catheter shaft,
such as by tapering the shaft or more abruptly reducing the diameter, e.g., by
connecting
(e.g., butt welding) a shaft having larger diameter to one having a smaller
diameter. By
increasing the diameter of the infusion lumen in that part of the vessel that
will
accommodate a larger diameter shaft, there is a decreased resistance to fluid
flow than
would be the case if a fixed diameter infusion lumen (equal in diameter to
that used at the
distal tip of the device) were used along the entire length of the device.
Such a
configuration allows desired flow rates to be achieved while maintaining
relatively low
pressures, even when the diameter of the distal infusion lumen is small.
[0050] An alternative means of providing high flush rates while maintaining a
low
cross section in the light treatment zone is illustrated in FIGS. 12A, 12B and
12C. Here,
the device has a larger diameter shaft proximal to the light treatment zone 6
and a smaller
diameter shaft in the region of the light treatment zone 6 to allow the distal
end of the
device, which contains the diffuser 15, to be inserted into smaller diameter
vessels. In the
illustrated embodiment, the shaft reduces diameter at transition 39, which
separates the
distal end of the shaft into a proximal portion 2a and a distal portion 2b.
Six lumens pass
through the proximal portion 2a, with four of the six continuing through light
treatment
zone 6 via distal portion 2b. The continuing lumens distal to the transition
39 are a fiber
lumen 14, infusion lumens 4b, and guidewire lumen 18. Where the reduction of
six
lumens to four lumens occurs, the two lumens that terminate are infusion
lumens 4a.
28
CA 02495562 2005-02-02
These two infusion lumens 4a terminate at infusion ports 5a and 5b, such that
the flush
stream originating from these ports is directed distally towards the light
treatment zone 6.
Infusion ports 5c and 5d can also be provided to direct flush fluid sideways
toward the
vessel wall. If very small vessels are to be treated, the shaft diameter can
be reduced
further by using a common guidewire and fiber lumen in both the proximal
catheter shaft
2a and the distal catheter shaft 2b, or by eliminating the infusion lumens 4b.
Alternatively, to accommodate the requirements that infusion lumens 4b have
small
diameters, these infusion lumens can have a significantly larger diameter at
the proximal
end of the catheter and transition down to a smaller diameter proximal of the
occlusion
balloon as described in connection with FIGS. 11A, 11B and 11C.
[0051] FIGS. 13A, 13B and 13C illustrate an embodiment in which a single
infusion
lumen 4 terminates just proximal to the light treatment zone 6. Infusion lumen
4 may
have one or more infusion ports. Tnfusion ports may be directed in the forward
direction,
sideways direction or both. In the illustrated embodiment, infusion port 5a is
directed in
the forward direction and infusion port 5c is directed in the sideways
direction toward the
vessel wall.
[0052] FIGS. 14A, 14B andl4C illustrate an embodiment of the catheter having
two
infusion lumens, wherein one infusion lumen terminates proximal to the light
treatment
zone while the other continues to the distal end of the light treatment zone
to provide
multiple infusion ports along the length of the light treatment zone. Infusion
lumen 4a
terminates at the proximal end of the light treatment zone 6 and the infusion
lumen 4b
terminates at the distal end of the light treatment zone 6. Lumen 4b has
multiple infusion
ports 5 located throughout the length of the light treatment zone 6.
29
CA 02495562 2005-02-02
[0053] FIGS. 15A, 15B and 15C illustrate an embodiment where the distal end of
the
catheter shaft is reduced in diameter, similar to that described in the
previous figures,
except here the occlusion balloon 8 is located on the distal end and the
infusion lumens 4
terminate near the distal end of the light treatment zone 6. This embodiment
incorporates
infusion lumens 4 having multiple ports 5 located along the length of the
light treatment
zone 6 with the distal end of the lumens 4 open to allow fluid to be delivered
from the
end of these lumens. As can be seen from examining the other f gores, multiple
combinations can be used here, examples of which are: distal end of lumens
sealed with
multiple ports throughout light treatment zone, no ports throughout the light
treatment
zone with only the distal ends of lumens open to provide flush ports, multiple
flush ports
alternately spaced on the different lumens throughout the light treatment
zone, only a
single infusion lumen instead of two, etc. Also, in this embodiment and
several previous
illustrations, the fiber lumen and inflation lumen are combined to utilize a
common
lumen. Alternatively, in this and previously illustrated embodiments, separate
lumens
could also be used for the fiber and inflation of the occlusion balloon.
Similarly, one or
multiple infusion lumens can be used, although it is preferable to use at
least two lumens
in this design to ensure that flush is directed somewhat symmetrically around
the catheter
shaft. Similarly, the infusion lumens may have diameters that are larger at
the proximal
end of the catheter than at the distal end to allow higher pressures and
associated higher
infusion rates to be delivered at infusion ports 5, as described in
conjunction with FIGS.
11A, 11B and 11C.
[0054] As illustrated in FIGS. 16A, 16B, and I6C, the catheter can also be
constructed
as a shaft within a shaft. In this embodiment the inner shaft 2b is comprised
of the
CA 02495562 2005-02-02
guidewire lumen 18 and fiber lumen 13. The inner shaft 2b is contained within
the
infusion lumen 4 of the outer shaft 2a. The outer shaft 2a also houses an
infusion lumen
4 and the inflation lumen 16. At the proximal end of the catheter 3 (shown in
FIG. 2), the
inner shaft 2b extends proximal to the outer shaft to allow the guidewire and
fiber to be
easily inserted. The inner shaft 2b also protrudes from the distal end of the
infusion
lumen 4 by a distance that is at least as long as the diffuser 15. The
occlusion balloon 8
is mounted on the distal end of the outer shaft 2a and is inflated and
deflated via the
inflation lumen 16 and inflation port I7. At the distal end, the outer shaft
and associated
infusion lumen 4 terminate just proximal to the diffuser 15. The infusion
lumen 4
provides a conduit for flushing media to be directed towards and around the
circumference of the fiber diffuser 15 in order to clear blood from the light
treatment
zone 6. Similarly, drugs can be locally delivered using this approach. To
maintain flush
output around the circumference of the fiber diffuser 15 and to prevent the
inner and
outer shafts from moving relative to each other, the two shafts can be
mechanically
connected near the distal end of the outer shaft 2a. This mechanical
connection is
preferably made in a manner that helps to center the inner shaft Zb within the
outer shaft
2a, but so as to not substantially block fluid flow. The mechanical connection
is
generally located within three centimeters of the distal end of the outer
shaft 2a. Various
means such as epoxy, heat bonds or mechanical ribs can be used to form the
connection.
[0055] A similar embodiment using coaxial shafts is shown in FIGS. 17A, 17B,
and
17C. The coaxial shafts used here are similar to those used in FIG. 16A-C,
except now
the outer shaft 2a continues to the distal end of the light treatment zone 6
where it is
connected to the inner shaft 2b as described above. The occlusion balloon 8 is
positioned
31
CA 02495562 2005-02-02
distal to the light treatment zone 6 and is inflated either with a dedicated
infusion lumen
(not shown) or with a common fiberlinflation lumen 14 as shown in FIG. 17A.
Infusion
ports 5 can be located such that infusion fluid flows from at the distal end
of the outer
shaft in the forward direction, from the distal end of the outer shaft but
directed sideways
toward the vessel wall, or from multiple ports located along the length of the
light
treatment zone. For illustration purposes, all of these possibilities are
shown in FIG.
17A. This design is advantageous when delivering the light near the proximal
end of a
larger diameter vessel.
[0056] FIG. 18 illustrates an alternative embodiment of the proximal end of
the
catheter. Intermediate point IOb connects to intermediate point l0a on distal
end 1
(shown in previous figures). Inflation port 40 connects to the inflation
Lumen. Infusion
input 42 connects to the infusion lumen. Optical fiber connector 52 connects
the light
guide to a light source. A guidewire is inserted into guidewire lumen 18
through
guidewire input port 46.
[0057] FIG. 19 illustrates another embodiment of the proximal end of the
catheter.
Inflation port 40 connects to the inflation Lumen. Infusion input 42 connects
to the
infusion lumen. Optical fiber connector 52 connects the light guide to a light
source. A
guidewire is inserted into guidewire lumen 18 through guidewire input port 46.
All input
ports connect to the shaft via common port 54.
(0058] The occlusion/infusion catheters described here can be used in a
variety of
ways. For example, since the flow rate of the flush is relatively Low, the
flush can be
initiated prior to inserting the catheter into the body and can be Left on for
the entire
32
CA 02495562 2005-02-02
procedure. With this approach the operator is only responsible for inflating
and deflating
the occlusion balloon. Alternatively, the flush can be used only when the
device is
positioned or only when the occlusion balloon is inflated. One or more boluses
of flush
fluid can be infused immediately after inflation of the occlusion balloon.
This tends to
quickly clear the blood from the light treatment zone, thereby maximizing the
amount of
light that can be delivered to the vessel wall in a given period of time.
Since the
occlusion balloon blocks blood flow, there is a minimal amount of blood
entering the
light treatment field from the proximal (as defined by the nominal direction
of blood
flow) side of the vessel. Furthermore, because the back-pressure from the
venous side is
relatively low, there is minimal blood entering from the distal region of the
vessel.
However, in practice it may be beneficial to provide a continuous low pressure
flush
throughout the period of the light treatment. This maintains a positive
pressure in the
vessel within the light treatment field, thereby helping to prevent blood from
flowing
back into the light treatment field. Furthermore, continuous flow helps to
sweep away
any small amounts of blood that may enter the light treatment zone via leakage
around
the occlusion balloon or by similar means. Of course, there are a multitude of
similar
methods by which the flush fluid can be delivered, similar to those described
above.
[0059] The unexpected improvement in treatment outcome that can be obtained
using
the devices and methods described above, relative to previous approaches,
results in part
from better elimination of blood with reduced risk of mechanical trauma to the
vessel.
While the benefit of improved blood elimination is most pronounced at shorter
wavelengths where light attenuation by blood is most significant, it exists
for longer
33
CA 02495562 2005-02-02
wavelengths as well since blood also significantly attenuates light throughout
the visible
and infrared portions of the spectrum.
[0060] One reason why the improved outcome achieved by the devices and methods
described herein was unexpected is the perception concerning the importance of
centering the source within the vessel. One of the purported advantages of the
angioplasty balloon approach is the ability of that approach to center the
light source
within the vessel. However, the biological response when using the
occlusionlinfusion
design displays good circumferential uniformity regardless of how well the
source is
centered. However, this circumferential uniformity is only present when blood
is
efficiently eliminated from the light treatment zone. Based on these
characteristics, the
circumferential uniformity seen with the occlusion/infusion design is Iilcely
due to the
combination of the light scattering characteristics of tissue and the
efficient elimination of
blood. Since tissue tends to strongly scatter light, placing a light source
within a vessel is
analogous to placing it within an optical integrating sphere. For example, if
the Iight
source is off center, it will deliver a higher irradiance to the vessel wall
which lies nearest
to it, with the lowest irradiance being delivered to the vessel wall that lies
farthest away.
However, the scattering properties of the tissue will cause much of the light
from the
nearest wall to be scattered to the farthest and vice versa. The net result is
a significantly
more homogeneous distribution of light within the vessel wall when the source
is off
center than might otherwise be expected. However, this effect is only achieved
if blood
is efficiently eliminated from the light treatment zone, since this blood
would otherwise
tend to absorb the light before it could scatter sufficiently to achieve a
homogeneous light
distribution. As a result, the occlusion/infusion design approach delivers a
more uniform
34
CA 02495562 2005-02-02
light dose than would be achieved with bare fiber approaches used previously
since these
do not provide the means to eliminate blood. While this light homogenizing
effect of
tissue will not provide the same degree of uniformity as would be obtained
from a
perfectly centered light source, the biological result obtained by such a non-
centered
source is insignificant, contrary to what has been describedin the prior art.
[006I] In addition to the biological results described above, the catheters
described
herein provide the additional advantage of allowing the user to leave the
guidewire in
place during light delivery. Previous designs have either attempted to use
concentric
diffusers and guidewires, or have relied on the user removing the guidewire
prior to light
treatment. By efficiently eliminating blood and thereby allowing significant
light
scattering without significant absorption of light by blood, the need to
either remove the
guidewire or use a concentric diffuser and guidewire can be avoided. This
simplifies the
device design and results in a safer clinical procedure.
[0062] Another benefit of the occlusion/infusion design over the angioplasty
balloon
design results from the materials used in balloon fabrication. The
occlusion/infusion
approach avoids the inflation problems associated with the combination of a
balloon
having a long length and non-compliant balloon shape. In practice it is
difficult to
fabricate practical compliant balloons having lengths that are much larger
than their
diameters since such balloons have a tendency to not inflate uniformly over a
long length.
(Even if such a balloon could be fabricated it would still trap a thin layer
of blood
between the balloon and the vessel wall, particularly in vessels containing
stems or other
complex morphologies.) With the occlusionlinfusion approach, a balloon having
a short
length is inflated either proximal or distal to the light treatment zone.
Since the only
CA 02495562 2005-02-02
requirement is for the inflated balloon to block blood flow, this balloon can
have a very
short length as opposed to the angioplasty balloon approach. Furthermore, it
is not
necessary that this occlusion balloon inflate uniformly since the need to have
the light
source centered within the vessel is eliminated. Consequently, a compliant
(more elastic)
material can be used to fabricate the balloon, which prevents minimal risk of
mechanical
damage even when the balloon is over-inflated. This benefit is a result of the
compliant
nature of elastic balloon materials.
[0063] A further benefit of using a compliant occlusion balloon is reduced
risk of
mechanical damage if the balloon is inadvertently over-inflated. If such over-
inflation
occurs with a compliant balloon it tends to expand along the length of the
vessel, rather
than outward. However, a non-compliant balloon would tend to expand outward,
thereby
risking mechanical damage to the vessel.
[0064] However, a non-elastic balloon can also be used with the catheters
disclosed
herein as long as it is properly sized to the vessel and over-inflation is
avoided. In either
case it is important to note that the purpose of the balloon used in the
occlusion/infusion
catheter is simply to block or significantly reduce blood flow, unlike the
angioplasty
balloon design where the balloon must eliminate blood by displacing it. A
significant
risk associated with non-elastic balloons--the tendency to cause mechanical
vessel
damage when inflated over a long length in tortuous or tapering vessels--can
be avoided
since an occlusion balloon can be of a short length and low pressure.
[0065] The integrated diffuser tipped fiber also provides significant
advantages over
prior fiber optic devices that emit light at essentially a single point. Use
of a fiber that
36
CA 02495562 2005-02-02
emits light at a single point requires that the operator mechanically slide
the fiber relative
to the catheter in order to achieve light treatment along a length of vessel.
The need for
such manual operation is eliminated by inclusion of a diffuser as described
herein.
Furthermore, by integrating the fiber into the catheter in a fixed manner, as
described in
some of the designs disclosed here, the operator can position a single fully
integrated
catheter and does not have the burden of separately positioning the catheter
and the light
delivery fiber. Finally, this integrated approach allows the use of more
flexible f hers
since there is no need for requirement for fiber to be stiff enough that the
operator can
insert it to the distal end of the catheter. This results in a catheter that
is more flexible
overall, and, consequently, better able to access more distal blood vessels.
[0066] In addition to the unexpected performance cited above, the catheter
design and
methods described herein provide additional advantages over previous
approaches. As
described above, when using the angioplasty balloon approach, the balloon can
cause
mechanical trauma to the vessel wall along the length of the inflated
angioplasty balloon,
due to the non-compliant nature of the balloon as described above. The
resulting injury
response can result in undesirable outcomes, such as development of intimal
hyperplasia,
which causes restenosis. Since cardiovascular FDT is designed to inhibit such
injury
responses, this is not a significant drawback as Iong as a sufficiently high
light dose is
delivered to the vessel wall. Unfortunately, such a sufficient light dose
cannot be
delivered at the ends of the balloon since the light can only be delivered
over the length
of the diffuser but not at the ends of the balloon where blood is present.
This prevents an
adequate light dose from being delivered at the ends of the balloon and would
be
expected to result in the edge effects seen with other cardiovascular
treatments, including
37
CA 02495562 2005-02-02
drug-coated stems and brachytherapy. Since the occlusion/infusion design
eliminates
blood from either end of the light source and, more importantly, does not
induce
mechanical trauma within the region of the light treatment zone, the
likelihood of such
edge effects is significantly reduced. While the occlusion balloon inflated at
either end of
the light treatment zone could potentially induce mechanical trauma, this is
highly
unlikely with properly designed compliant balloons. Furthermore, this is also
unlikely
when using a non-compliant occlusion balloon as described here as long as the
balloon is
properly sized. The reason for such a reduced risk of damage from a non-
compliant
occlusion balloon is that since it is very short it does not have the
drawbacks associated
with inflation over a long length in tortuous or tapering vessels as described
above for
conventional angioplasty balloon designs. Other promising applications include
the
treatment of atherosclerosis by causing the size of the plaque to regress and
stabilization
of vulnerable plaque and aneurysm through elimination of inflammation. In all
these
cases it is highly desired that the target treatment site not undergo
mechanical trauma
since such trauma could exacerbate the existing disease. The
occlusion/infusion
approach used here achieves that goal since, unlike previous approaches, this
approach
avoids mechanical contact with the target treatment site.
[0067] Another advantage of the devices and methods described herein is
reduced
mechanical trauma within the light treatment field. One of the applications of
PDT is the
treatment of angioplasty sites within a vessel to inhibit a restenotic injury
response.
However, to achieve an appropriate biological inhibition response with PDT it
is
necessary to deliver the PDT treatment beyond either end of the angioplasty
zone. When
using a modified angioplasty balloon to displace blood and deliver light, a
longer balloon
3~
CA 02495562 2005-02-02
is required for light delivery than is used for the balloon angioplasty in
order to
effectively deliver light beyond either side of the angioplasty region. Use of
such a
longer balloon also minimizes the risk of misalignment between the angioplasty
treatment site and the delivered light dose. However, use of such an
angioplasty style
light delivery balloon that is longer than the angioplasty balloon risks
introducing
additional trauma to the vessel wall, particularly in those regions of the
vessel beyond the
site of the angioplasty. Such a result, wherein the treatment therapy intended
to prevent
an injury response actually induces an injury response, is clearly
unacceptable.
j0068] Another advantage of this approach is improved ability to treat long
tortuous
vessels. When using a light-emitting element within a modified angioplasty
balloon it is
necessary to fully inflate the balloon to adequately displace blood to allow
adequate light
delivery. However, this can be difficult in tortuous vessels, especially if
the treatment
length is greater than 1-2 cm. This is due to the fact that, when inflated,
the non-
compliant, modified angioplasty balloon tends to inflate in a straight line,
rather than
follow the curvature of tortuous vessels. The result is that the balloon tends
to straighten
the vessel, resulting in undesired mechanical trauma to the vessel. This
limitation cannot
be overcome by under-inflation of the angioplasty style light delivery balloon
since under
inflation results in inadequate displacement of blood. The only effective
solution to this
problem is to use a short balloon (1-2 cm in length) and deliver the treatment
in a
stepwise manner, treating short sections of vessel with each step.
[0069] Another advantage of the catheter of the present invention is the
ability to treat
small diameter vessels. When using the modified angioplasty balloon approach,
it is
necessary to mount the non-compliant angioplasty balloon on the catheter shaft
39
CA 02495562 2005-02-02
overlapping the light treatment zone. However, use of such a non-compliant
balloon
adds to the overall device profile, thereby limiting access to small vessel
diameters.
Furthermore, the vessel diameter must be sufficiently large to allow for
inflation of the
balloon along its length. With the occlusionlinfusion approach disclosed the
balloon is
mounted away from the light treatment zone, generally well proximal to the
light
treatment zone. Consequently, since there is no need to locate a balloon at
the distal end
of the device, the ultimate diameter of the occlusion/infusion device can be
smaller
allowing treatment of smaller vessels.
[0070] Another advantage of the occlusion/infusion device is in the treatment
of vessels
whose diameter tapers or otherwise changes within the length of the section to
be treated.
When using a modified angioplasty style balloon it is necessary to inflate the
balloon to
displace the blood, which can lead to induction of significant injury within
the smaller
diameter regions of the vessel being treated. Since the occlusion/infusion
device does not
require inflation of such a balloon, this problem is avoided altogether.
Furthermore, the
occlusion balloon that is inflated on the occlusion/infusion device is either
compliant or,
even if non-compliant, is of a short length, typically on the order of 5 mm.
Therefore,
there is no similar limitation associated with inflation of the occlusion
balloon outside the
light treatment zone.
[0071] Another advantage of the devices described herein is their ability to
treat
multiple vessel diameters with a single device. With the modified angioplasty
balloon
approach the device must be correctly sized to the vessel to be treated. This
requires that
a significant stock of devices be kept on hand and also limits the various
vessel
geometries that can be treated. However, these limitations can be completely
avoided
CA 02495562 2005-02-02
with the occlusion/infusion style light delivery device using a compliant
balloon since the
compliant balloon allows a wide range of vessel diameters to be treated with a
single
device. Similarly, a single device can be used on a patient at multiple
locations within
the cardiovascular system unlike what would be the case with an angioplasty
balloon
approach.
[0072] Another advantage of the devices describe herein is the integration of
multiple
features. As described above, one or more occlusion balloons can be located on
the
catheter shaft, well outside the desired light treatment zone. Since these
balloons are
located well away from the light treatment zone, this allows other features to
be mounted
on that part of the catheter shaft overlapping the light treatment zone, as
described in U.S.
Application Ser. No. , entitled Catheter and Method for Diagnosis and
Treatment of Diseased Vessels, filed concurrently herewith and incorporated
herein by
reference in its entirety. Features that can be incorporated within this
portion of the
catheter shaft include a separate angioplasty style balloon, means for Iocal
drug delivery,
I S means to detect disease, etc.
[0073] In addition to the design improvements highlighted above, the light
delivery
catheter of the present invention can use multiple infusion ports to further
overcome the
shortcomings of prior light delivery catheter designs. When attempting to
displace blood
from a straight section of vessel using conventional flushing mechanisms,
there can be a
tendency for the fluid delivered from a given infusion port to preferentially
follow a
particular flow path. While this can provide effective blood elimination along
that
particular flow path, pockets of residual blood lying outside the primary flow
path can
remain. These blood pockets can compromise the efficacy of the treatment due
to
41
CA 02495562 2005-02-02
absorption of light. An even more significant problem arises when attempting
to treat a
vessel segment that includes a branch vessel, as is often the case in
practice. In the case
of such a branch, the flush fluid tends to flow along the length of the device
until it
reaches the branch, at which point the majority of the flush fluid flows down
the branch.
This results in inadequate flushing of the vessel segment beyond the branch
point. This
tendency of the fluid to flow down the branch vessel, rather than the intended
vessel, is a
result of the fact that the light delivery catheter can occupy a significant
portion of the
main vessel in which it is located. In this way the catheter can act to
provide higher flow
resistance in the main vessel than in the branch, hence a significant portion
of the flush
fluid passes down the lower resistance branch vessel leaving the main vessel,
which is the
target of the treatment, with insufficient flush to adequately clear the
blood.
[0074] An effective means for overcoming both of these limitations is to
locate multiple
infusion ports along the length of the catheter within the light treatment
zone. This
design can provide a significant benefit over a design in which flush is
delivered at a
fixed location along the length of the catheter. First of all, when fluid is
emitted from
multiple infusion ports along the length of the catheter, the previously
described tendency
for trapping of residual pockets of blood within the light treatment zone is
significantly
reduced. This leads to less attenuation of light by blood and a much more
uniform and
efficacious biological response. This benefit is particularly significant when
using short
wavelengths of light, particularly those for which absorption of light by
blood is high.
The additional infusion ports most likely increase flow turbulence, which
appears to help
dislodge pockets of blood. It is also likely that including infusion ports
along the length
of the device decreases the likelihood that the flushing fluid will establish
a preferred
42
CA 02495562 2005-02-02
flow path, which would lead to nonuniform flushing. Such mechanisms may be
responsible for improved flushing achieved by locating multiple infusion ports
along the
length of the light treatment zone, as opposed to having them at a single
location. This
improvement is significant in the case of vessels without branches and is
particularly
dramatic for vessels having branches within the vessel region to be flushed.
[0075] Although the invention has been described with reference to specifc
embodiments, it should be understood that various changes may be made without
departing from the spirit or scope of the invention. For instance, the various
features
described above and shown in the drawings can be used singly or in any of
various
combinations. Accordingly, the disclosed examples are intended to be
illustrative of the
scope of the invention and are not intended to be liriliting. The scope of the
invention is
defined as set forth in the appended claims.
43
